Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy

Version 1 : Received: 1 October 2020 / Approved: 2 October 2020 / Online: 2 October 2020 (09:21:53 CEST)

A peer-reviewed article of this Preprint also exists.

Falvo, E.; Arcovito, A.; Conti, G.; Cipolla, G.; Pitea, M.; Morea, V.; Damiani, V.; Sala, G.; Fracasso, G.; Ceci, P. Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy. Pharmaceutics 2020, 12, 992. Falvo, E.; Arcovito, A.; Conti, G.; Cipolla, G.; Pitea, M.; Morea, V.; Damiani, V.; Sala, G.; Fracasso, G.; Ceci, P. Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy. Pharmaceutics 2020, 12, 992.

Journal reference: Pharmaceutics 2020, 12, 992
DOI: 10.3390/pharmaceutics12100992

Abstract

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

Subject Areas

Nanomedicine; human ferritin; gastrointestinal tumors; non-camptothecin topoisomerase I inhibitors; drug-delivery; CD71

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